Resveratrol induces SIRT1-Dependent autophagy to prevent H2O2-Induced oxidative stress and apoptosis in HTR8/SVneo cells.

INTRODUCTION: Pre-eclampsia (PE) is a serious complication of pregnancy, and the likely pathogenic basis of early onset PE are placental dysfunction and increased oxidative stress. Resveratrol (RES) is a potent antioxidant which has shown beneficial effects in many diseases. The aim of this study was to investigate the protective effects of RES against oxidative stress-induced damage in trophoblasts, and elucidate the potential mechanisms. METHODS: We established an in vitro model of oxidative stress by exposing the human first-trimester extravillous trophoblast cell line HTR8/SVneo to H2O2. The level of oxidative stress was reflected by ROS, MDA and SOD. The viability of cells was determined by the MTS assay. Apoptosis was detected using Annexin V-FITC staining and flow cytometry. Levels of SIRT1(sirtuin 1) and autophagy-related proteins (LC3, Beclin-1, p62) were detected by western blot. Autophagosomes were observed by transmission electron microscopy (TEM). RESULTS: Pre-treatment with RES significantly ameliorated H2O2-induced cytotoxicity, morphological damage, oxidative stress and apoptosis. Mechanistically, RES restored the levels of SIRT1 and autophagy-related proteins including LC3-II, Beclin-1 and p62 that were dysregulated by H2O2. Blocking autophagy by 3-methyladenine (3-MA) completely abolished the protective effects of RES, as did knocking down SIRT1. CONCLUSION: RES may protect human trophoblasts against H2O2-induced oxidative stress by activating SIRT1-dependent autophagy, and therefore has therapeutic potential in PE.

RNAi­mediated downregulation of asparaginase­like protein 1 inhibits growth and promotes apoptosis of human cervical cancer line SiHa.

Asparaginase like 1 (ASRGL1) protein belongs to the N­terminal nucleophile group, cleaving the isoaspartyl­dipeptides and L­asparagine by adding water. It tends to be overexpressed in cancerous tumors including ovarian cancer and breast tumors. The present study assessed the potential ability of ASRGL1 as a molecular target in gene­based cervical cancer treatment. The protein expression level of ASRGL1 was determined in paraffin­embedded tumor specimen by immunohistochemistry. Additionally, in order to assess the activity of ASRGL1 during the process of cervical cancer cell multiplication, ASRGL1­short hairpin (sh) RNA­expressing lentivirus was established, which was used to infect SiHa cells. The Cellomics ArrayScan VT1 Reader identified the influence of downregulation on SiHa caused by RNA interference­intervened ASRGL1. Flow cytometric analysis was also performed to evaluate the influence. The cyclin dependent kinase (CDK2), cyclin A2, B­cell lymphoma 2 (Bcl­2) and Bcl­2­associated X protein (Bax) expression levels were assessed by western blot analysis. ASRGL1 was observed to be overexpressed in cervical cancer tissues when compared with the adjacent normal tissues. The knockdown of ASRGL1 in SiHa by ASRGL1­shRNA lentivirus infection significantly inhibited cell growth and enhanced cellular apoptosis; the cells were also captured during the S phase. The knockdown of ASRGL1 expression led to the increased expression of Bax and decreased expression of Bcl­2, CDK2 and cyclin A2. In conclusion, ASRGL1 was closely associated with growth and apoptosis in cervical cancer. Therefore, ASRGL1 may be a novel, potentially effective anti­cervical cancer therapy.

Optimal antithrombotic therapy in patients with atrial fibrillation following percutaneous coronary intervention: A systemic review and meta-analysis.

A challenge for antithrombotic treatment is patients who present with atrial fibrillation (AF) and acute coronary syndrome, particularly in patients who have undergone coronary percutaneous intervention with stenting (PCIS). In the present study, a total of nine observational trials published prior to July 2017 that investigated the effects of dual antiplatelet therapy (DAPT; aspirin + clopidogrel) and triple oral antithrombotic therapy (TOAT; DAPT + warfarin) among patients with AF concurrent to PCIS were collected from the Medline, Cochrane and Embase databases and conference proceedings of cardiology, gastroenterology and neurology meetings. A meta-analysis was performed using fixed- or random-effect models according to heterogeneity. The subgroups were also analyzed on the occurrence of major adverse cardiac events (MACE), stroke and bleeding events in the two treatment groups. Analysis of baseline characteristics indicated that there was no significant difference in the history of coexistent disease or conventional therapies between the DAPT and TOAT groups. The primary end point incidence was 2,588 patients in the DAPT group (n=13,773) and 871 patients in the TOAT group (n=5,262) following pooling of all nine trials. There was no statistically significant difference in the incidence of primary end points between the DAPT and TOAT groups. Odds ratio (OR)=0.96, 95% confidence interval (CI)=0.73-1.27, P=0.79, with heterogeneity between trials (I2=82%, P<0.00001). Subsequently, on subgroup analysis, the results indicated no increased risk of major bleeding or ischemic stroke in the DAPT or TOAT group. However, compared with the TOAT group, there was an apparent increased risk of MACE plus ischemic stroke in the DAPT group (OR=1.62, 95% CI=1.43-1.83, P<0.00001) with heterogeneity between trials (I2=70%, P=0.01). In conclusion, the present meta-analysis suggests that TOAT (aspirin + clopidogrel + warfarin) therapy for patients with AF concurrent to PCIS significantly reduced the risk of MACE and stroke compared with DAPT (aspirin + clopidogrel) therapy. Further randomized controlled clinical trials are required to confirm the efficacy of the optimal antithrombotic therapy in patients with AF following PCIS.

Bioinformatics analysis of time series gene expression in left ventricle (LV) with acute myocardial infarction (AMI).

This study is to investigate the key genes and their possible function in acute myocardial infarction (AMI). The data of GSE4648 downloaded from the Gene Expression Omnibus (GEO) database include 6 time points (15 min, 60 min, 4h, 12h, 24h and 48 h) of 12 left ventricle (LV) samples, 12 surviving LV free wall (FW) samples, 12 inter-ventricular septum (IVS) samples after AMI operation and corresponding sham-operated samples. The data of each sample were analyzed with Affy and Bioconductor packages, and differentially expressed genes (DEGs) were screened out using BETR package with false discovery rate (FDR)<0.01. Then, functional enrichment analysis for DEGs was conducted with Database for Annotation, Visualization and Integrated Discovery (DAVID). Totally 194 DEGs were identified in LV, and only the gene tubulin beta 2a (Tubb2a) and natriuretic peptide B (Nppb) were respectively up-regulated in surviving FW tissue and IVS tissue. The biological process response to wounding and inflammatory response were significantly enriched, as well as leukocyte transendothelial migration pathway. Besides, the expression pattern analysis showed the DEGs mostly up-regulated at 4h after AMI, and these genes were mainly associated with immunity. Additionally, in transcriptional regulatory network, early growth response 1 (Egr1), activating transcription factor 3 (Atf3), Atf4, Myc and Fos were considered as the key transcription factors related to immune response. The key transcription factors and potential target genes might provide new information for the development of AMI, and leukocyte transendothelial migration pathway might play a vital role in AMI.

[Spatiotemporal dynamics of land use in Langqi Island at Minjiang Estuary].

By using RS and GIS techniques and a series of indices in characterizing the dynamics of land use, the spatiotemporal characteristics of land use in Langqi Island at Minjiang Estuary in 1989, 1996 and 2005 was studied. The results showed that in 1989-2005, the land use types in the Island all changed, but agricultural landscape was always the main land type. The single land use dynamics of water area was the largest, which reached 7.85% from 1989 to 2005. The annual change rate of comprehensive land use was 1.90%, the cultivation rate decreased rapidly, while the forest coverage and the construction land use rate increased. The comprehensive index of land use degree in the study area decreased, which indicated that the land use type tended to be diversification.